This research is a study in cancer drug development, involving the total synthesis of N-isosteres of antitumor anthracyclines, in which quinone C=O groups are replaced by N-oxide. These isosteres will be the first anthracycline analogs that provide changes in the C skeleton of theaglycone. The changes will be specifically at the quinone, a key site of action in several proposed biochemical mechanisms, based on he redox and radical-generating properties or the alkylating action of the quinone. These mechanisms may be related to antitumor activity or cardiotoxicity, or both, and the isosteres may be expected to give a separation of these effects. The synthetic approach is to convert substituted phenazines to 7,8,9,10-tetrahydrobenzo[b]phenazine di N-oxides isosteric with anthracylinones, followed by coupling with daunosamine. Products will be screened for antitumor activity at NCI and tested in vitro for DNA interactive properties and stimulation of O2 consumption by mammalian microsomes. Active products will be tested for cardiotoxicity by measuring ECG changes in the rat. S-isosteres of the active products will also by synthesized. The ultimate objective is better cancer drugs. The potential of the anthracycline class has not been exploited until such changes are tried.